Intricate synthetic and natural organic bioactive molecules typically include a hydrocarbon skeleton containing a large number of aliphatic C—H bonds. The hydrocarbon skeleton is often decorated with oxidized functionalities, for example, carbons functionalized with oxygen and/or nitrogen containing groups. The identity and position of the oxidized functionalities strongly affect the biological activity of the molecule. Reactions that selectively introduce an oxidized functionality into an organic framework are therefore of particular significance in the synthesis of bioactive molecules.
Certain general reaction classes have emerged for introducing oxidized functionality into organic frameworks. These reaction classes include functional group interconversions, carbon-carbon bond forming reactions of pre-oxidized fragments, and olefin oxidations. Using these reactions, modern synthetic planning often focuses on the use and maintenance of oxidized functionalities once they have been introduced into the molecule.
In contrast, iron enzymes can perform catalytic, selective oxidations of isolated sp3-hybridized C—H bonds in intricate molecules. Examples of these iron-containing enzymes include cytochrome P-450 and methane monooxygenase (MMO). The selective reactivity of such natural catalysts is dependent on elaborate protein binding pockets. Although binding pockets provide enzymes with good specificity and reactivity, they also limit the general applicability of the enzymes in the oxidation of a broad range of substrate molecules.
A major challenge in developing a useful oxidation reaction for intricate molecules is to develop a reaction system that is both highly reactive and predictably selective for oxidation of relatively inert and ubiquitous C—H bonds. Moreover, to be useful in intricate molecule synthesis, the reaction system would preferably have reactivity and selectivity that is general for a broad range of substrates. Such a reaction system could streamline complicated syntheses by providing methods to install oxidized functionalities at a late stage, thereby reducing unproductive chemical transformations associated with carrying the functionalities throughout a synthetic procedure. Furthermore, the reaction system would preferably rely on catalyst control as opposed to substrate control to broaden its synthetic applicability.